Hepatic Impairment
Conditions
Brief summary
The primary purpose of the study is to determine the effect of mild, moderate, and severe hepatic impairment on the PK of total treprostinil palmitil (TP) and treprostinil (TRE) following a single dose of 80 micrograms (μg) TPIP, when compared to normal hepatic function.
Interventions
Oral inhalation using a dry powder inhaler device.
Sponsors
Insmed Incorporated
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
* Body mass index between 18.0 and 40.0 kilograms per square meter (kg/m\^2), inclusive. Inclusion Criteria for Participants with Normal Hepatic Function * In good health, as determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs measurements, and clinical laboratory assessments (congenital nonhemolytic hyperbilirubinemia \[eg, suspicion of Gilbert's syndrome based on total and direct bilirubin\] is not acceptable) at screening and check-in, as assessed by the investigator (or designee). Inclusion Criteria for Participants With Hepatic Impairment: * Diagnosis of chronic (\>6 months), stable hepatic impairment with no clinically significant changes within 30 days prior to dosing, as determined by medical history. * Participants with type 2 diabetes mellitus may be included, if they have: * glycosylated hemoglobin A1C ≤8.5% at screening * fasting blood glucose ≤240 milligrams per deciliter (mg/dL), while participant is using their normal diabetes medication, at screening and check-in.
Exclusion criteria
* History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair are allowed). * Use or intend to use any moderate or strong inducers or inhibitors of CYP2C8 or CYP2C9 within 30 days prior to dosing. * Participation in a clinical trial involving administration of an investigational medicinal product (IMP) (new chemical entity) in the past 30 days or 5 half-lives of that drug (if known) prior to dosing, whichever is longer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Treprostinil Palmitil (TP) and Treprostinil (TRE) | Pre-dose and at multiple timepoints post-dose up to Day 3 | Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function. |
| Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of TP and TRE | Pre-dose and at multiple timepoints post-dose up to Day 3 | Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function. |
| Maximum Observed Plasma Concentration (Cmax) of TP and TRE | Pre-dose and at multiple timepoints post-dose up to Day 3 | Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function. |
| Apparent Total Clearance (CL/F) of TP and TRE | Pre-dose and at multiple timepoints post-dose up to Day 3 | Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function. |
| Apparent Terminal Elimination Half-Life (t1/2) of TP and TRE | Pre-dose and at multiple timepoints post-dose up to Day 3 | Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function. |
| Time to Maximum Observed Concentration (Tmax) of TP and TRE | Pre-dose and at multiple timepoints post-dose up to Day 3 | Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function. |
| Apparent Volume of Distribution (Vz/F) of TP and TRE | Pre-dose and at multiple timepoints post-dose up to Day 3 | Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fraction Unbound (Fu) of TRE | Pre-dose and at multiple timepoints post-dose on Days 1 and 2 | Determination of the effect of mild, moderate, and severe hepatic impairment on the unbound PK of TRE following a single dose of TPIP, when compared to normal hepatic function. |
| Number of Participants Who Experienced At Least One Adverse Event (AE) | Up to Day 7 | Evaluation of safety and tolerability of a single dose of TPIP in participants with mild, moderate, and severe hepatic impairment and normal hepatic function. |
Countries
United States
Contacts
CONTACTInsmed Medical Information
STUDY_DIRECTORStudy Director
Insmed Incorporated
Outcome results
None listed